Ochem Reactions

Decarboxylation

• works with b-keto acids and b-dicarbox acids

• -CO₂ and heat

Halogenation (Acidic)

• Br₂ or Cl or I + HCl

• installs to one Alpha Hydrogen Only

Halogenation (Basic)

• Br₂ or Cl or I + NaOH

• Installs to all alpha hydrogens your attacking at

HVZ Reaction

• works with alcohol groups or carboxylic acids

• 1. PBr₃, Br₂

• 2. H₂O work up

• replaces -OH group and ads to one alpha hydrogen

Alpha Halogen Substitution

• replaces the halide with weak base

• SN2 reaction

• Uses a Carboxylate Ion or like NaCOOR

Alkylating Enolates

• works on Aldehydes, Ketones, Esters, and Nitriles

• 1. LDA force enolate

• 2. do an SN2 with a R-BR

• racemic mixture

Alkylating Enamines

• Make Enamine first

• do an SN2 or SNAC reaction (R-Br)

• Hydrolyze (HCl + H20)

Alkylating Beta-Carbon

• weak base Nu: (1-2 addition)

• done by Beta Carbons on enamines

• react with a aldehyde/ketone with an alkene

• then hydrolyze (HCl + H20)

Michael Reactions

• contains enolate with 2 EWG so like two ketones or Esters

• reacts with an aldehyde or ketone with an alkene at the end

• use weak base conditions such as NaOH + H2O or like NaOMe + MeOH

Aldol Addition

• weakly basic conditions such as NaOH + H2O

• works with aldehydes or ketones (2 of the same ones)

Retro - Aldol Addition

• heat + NaOH and H2O

Dehydration of Adols

• works with alpha/beta unsaturated aldehydes and ketones

• acid (HCl + heat) or base (NaOH + Heat)

• makes an enone

Crossed Adol

• two different groups

• if one has no alpha-Hs then we add it slowly and do HCl workup

• if both have alpha-Hs force enolate with LDA and add Electrophile slowly with HCl w/u

Claisen Condensation

• gives Beta-keto esters

• uses two of the same esters!

• needs two alpha-Hs on enolate ester

• Weakly basic conditions os NaOMe and then acid work up (HCl)

• needs to go through the second enolate!!!!

Crossed Claisen

• two different ester groups

• weakly basic conditions (NaOMe and MeOH)

• Nu: is added slowly in weak base (NaOMe) then acid workup

Aldehydes + Ketones

• Weakly Basic conditions (NaOH + H20)

• two of the same aldehydes + ketones

• forms B-hydroxy aldehydes + ketones

Formate Esters + Ketones

• Gives us B-keto aldehydes

• ketone acts as Nu: with HCl workup

• Weakly basic conditions for formate like NaOEt

Ketones + Carbonates

• gives us B-keto esters

• ketone acts as Nu: slowly with HCl w/u

• Carbonate in weak base NaOEt

Ketones + esters

• form B-diketones

• force enolate with LDA

• then electrophile adds slowly with HCl w/u

Intramolecular Condensations

• only favors 5-6 rings

• gives cyclic B-keto esters

• weakly basic conditions (1. NaOMe and 2. HCl w/u

• count your carbons

Robinson Annulation

• combines Michael + Intra Aldo Addition + and a Dehydration

• involves Nu: with two EWG (ketones/esters)

• electrophile that is aldehyde/ketone/esters with an alkene for a (1-2 addition)

• Then, NaOH and MeOH

• Lastly, Heat + H2O to dehydrate

Malonic Ester Synthesis

• makes mono- or di-alkylated acetic acids

• uses a diethyl malonate

• reagents are

  • 1. NaOR, ROH

  • 2. RBr (SN2)

  • 3. HCl, H₂O, Heat

Acetoacetic Ester Synthesis

• uses ethyl acetoacetate

• makes mono or di-alkylated methyl ketones

• reagents:

  • 1. NaOR, ROH

  • 2. RBr

  • 3. HCl, H2O, Heat

Benzene Halogenation

• uses benzene as nucleophile

• reagents

  • X₂

  • FeX₃

• doesnt use Flourine or Iodine

• Need to use heat if with bromine not chlorine

Benzene Nitration

• uses benzene as nucleophile

• reagents

  • conc. HNO3

  • conc. H2SO4, heat

• have to make nitronium electrophile first

• adds a nitrate group to it (NO2)

Benzene Sulfonation

• uses benzene as nucleophile

• reagents

  • conc. H2SO4

  • heat

• need to make sulfonium ion first in mechanism

• adds a sulfonic acid group on benzene

Sulfonation as Protective Group

• can use the same reagents to protect it as a sulfonation

• to reverse it use

  • dilut. H2SO4

  • H2O

  • Heat

Friedel-Crafts Acylation

• benzene as nucleophile

• Reagents

  • 1. Either Acyl Chloride or Anyhydride with AlCl3

  • 2. H2O work-up

• adds an acyl group / ketone

• need to make acylium ion first

• need Xs catalyst (H2O)

Gattermann-Koch reaction

• done “in-situ”

• benzene as nucleophile

• reagents

  • 1. CO, HCl, AlCl3, CuCl

  • 2. Water work up

• makes us a aryl aldehyde

Friedel Crafts Alkylation

• benzene (xs) as nucleophile

• reagents

  • RX (halide)

  • AlX3

• no water work up

• make carbocation to add to ring first for mechanism

Alkenes Alkylating Benzene

• can alkylate benzene w/ strong acids present

• need H2SO4

Alcohols Alkylating Benzenes

• need presence of strong acid

• reagent

  • BF3 or H2SO4

  • heat

Friedel Crafts Alkylation Limitations

• will rearrange to become a more stable carbocation

• dont work on deactivated rings (such as ones that are alkylated already?)

• doesn’t work with aryl and vinylic halides (unstable)

• Without xs benzene, will add more than one alkyl group

Alkylation by Acylation Reduction

• benzene as nucleophile + acyl chloride

• reagents

  • 1. AlCl3

  • H2O

• reduces after attachment to get alkane / alkyl group

• causes for no rearrangement

Acylation Reduction (H2 + Pd/C)

• works with aryl ketones

• H2 + Pd/c reduces non-selectively

• becomes alkyl (alkane)

Wolff-Kishner

• works with aryl ketones

• reagents

  • NH2NH2, NaOH

  • heat

• not selective, will reduce all ketones

• very strong reducing agent

Clemmensen Reduction

• works only on aryl ketones

• reagents

  • Zn/Hg, HCl

  • heat

• works selectively !!

Alkylation via Coupling (OrganoCuperates)

• works with alcohol groups

• reagents

  • 1. PBr3, pyr

  • 2. Li, Hexane

  • 3. CuI, ether

• then couple with halogenated benzene ring (benzene with halide on it)

Oxidation of Arene Side Chain

• 1. KMnO4, NaOH, heat

• 2. HCl w/u

Benzene Nitration Reduction

• reduces to an amine

• reagents can either be with these

  • H2 + Pd/C

  • Fe + HCl

  • 1. LiAlH4 + 2. H2O w/u

Substitution of Benzenes

• alkylated benzenes involved

• reagents

  • Br2 + hv

  • NaCN (strong base)

• gives us a substitution

Elimination of Benzenes

• alkylated benzenes involved

• reagents

  • Br2 + hv

  • NaOtBu (strong + bulky base)

• gives us alkene